Axial functionalisation of photoactive diazido platinum(iv) anticancer complexes.

Mono-axial functionalised octahedral diazido Pt(iv) complexes trans, trans, trans-[Pt(py)(N)(OR)(OR)] (OR = OH and OR = anticancer agent coumarin-3 carboxylate (cou, ), pyruvate dehydrogenase kinase (PDK) inhibitors 4-phenylbutyrate (PhB, ) or dichloroacetate (DCA, )), and their di-axial functionalised analogues with OR = DCA and OR = cou (), PhB (), or DCA () have been synthesised and characterised, including the X-ray crystal structures of complexes and . These complexes exhibit dark stability and have the potential to generate cytotoxic Pt(ii) species and free radicals selectively in cancer cells when irradiated. Mono-functionalised complexes showed higher aqueous solubility and more negative reduction potentials. Mono- and di-functionalised complexes displayed higher photocytotoxicity with blue light (1 h, 465 nm, 4.8 mW cm) than the parent dihydroxido complex 1 (OR = OR = OH) in A2780 human ovarian (IC 0.9-2.9 μM for ; 0.11-0.39 μM for ) and A549 human lung cancer cells (5.4-7.8 μM for ; 1.2-2.6 μM for ) with satisfactory dark stability. Notably, no apparent dark cytotoxicity was observed in healthy lung MRC-5 fibroblasts for all complexes (IC > 20 μM). Significantly higher platinum cellular accumulation and photo-generated ROS levels were observed for the di-functionalised complexes compared with their mono-functionalised analogues when cancer cells were treated under the same concentrations.